The assessment of molecular/cellular pathophysiology and the development of neuroimaging for spinal cord-related pain

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10817
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Fukui
• Principal Investigator: Nakajima Hideaki 福井大学, 学術研究院医学系部門, 講師 (10397276)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脊髄障害性疼痛 / 神経障害性疼痛 / ニューロイメージング / PK1195 / PET / マイクログリア / マクロファージ

Outline of Final Research Achievements

We performed experiments on animal model and clinical study to aim to make visible the microglia activation by neuroimaging. PK11195 is antagonist of peripheral benzodiazepine receptor (PBR) that migrate to cell membrane depending on the microglia activation in response to spinal cord dysfunction.
In the animal model, PBR positive cells were colocalized with CD11b and iba-1. Most of PBR-positive cells were not merged with GFP-positive cells. In autoradiography, accumulation of PK11195 was identified after injury. In the clinical study, no uptake was seen in the healthy volunteer and the uptake was seen only in patients within one year after the neuropathic pain onset. Our results suggest that PBR is mainly located in activated microglia, and [11C]-PK11195 PET/MRI imaging is available to investigate whether microglial activation is evident in for the patients with neuropathic pain.

Free Research Field

脊椎脊髄病学

Academic Significance and Societal Importance of the Research Achievements

末梢神経損傷による神経障害性疼痛については、その病因メカニズムが研究されている一方で、脊髄実質の損傷による脊髄障害性疼痛発現の病態については未だ不明な点が多い。本研究では、GFP マウスの骨髄細胞移植のキメラマウスとを用いることで、脊髄由来あるいは骨髄由来のmicroglia/macrophgeを区別してそれぞれの役割を明らかにする。また11C-(R)PK11195-PET は活性型ミクログリアの可視化と報告されており、脳－脊髄の活性化ミクログリアの動態を捉えることができれば、この病態解明や治療効果判定など臨床的な面からも多大の貢献を成すものと考えられる。